Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
BMC Gastroenterol. 2023 May 19;23(1):163. doi: 10.1186/s12876-023-02812-5.
Anti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1β) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1β in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy.
Huh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1β to validate the antiviral activity of IL-1β. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1β and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant.
In vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1β and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1β in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1β showed an upward trend at 12w and 24w in the ERG. IL-1β significantly reduced HBV replication levels in hepatoma cells.
The increased expression of IL-1β may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.
抗乙型肝炎病毒 (HBV) 治疗使用富马酸替诺福韦二吡呋酯 (TDF) 联合聚乙二醇干扰素-α (Peg-IFN-α)，其疗效优于 TDF/Peg-IFN-α 单药治疗。我们之前的研究表明，白细胞介素-1β (IL-1β) 与 IFN-α 治疗慢性乙型肝炎 (CHB) 患者的疗效相关。本研究旨在研究 Peg-IFN-α 联合 TDF 与 TDF/Peg-IFN-α 单药治疗 CHB 患者时 IL-1β 的表达情况。
用 Peg-IFN-α 和/或替诺福韦（TFV）刺激感染 HBV 的 Huh7 细胞 24 小时。一项前瞻性招募 CHB 患者的单中心队列研究：未经治疗的 CHB（A 组）、TDF 联合 Peg-IFN-α 治疗（B 组）、Peg-IFN-α 单药治疗（C 组）、TDF 单药治疗（D 组）。正常供体作为对照。在 0、12 和 24 周收集患者的临床数据和血液。根据早期应答标准，B 组和 C 组分为早期应答组 (ERG) 和非早期应答组 (NERG)。用 IL-1β 刺激 HBV 感染的肝癌细胞，验证 IL-1β 的抗病毒活性。用酶联免疫吸附试验 (ELISA) 和实时荧光定量聚合酶链反应 (qRT-PCR) 检测血液样本、细胞培养上清液和细胞裂解液，评估各种治疗方案中 IL-1β 和 HBV 复制水平的表达。使用 SPSS 26.0 和 GraphPad Prism 8.0.2 软件进行统计分析。P 值<0.05 被认为具有统计学意义。
体外实验显示，Peg-IFN-α 联合 TFV 治疗组的 IL-1β 表达水平更高，对 HBV 的抑制作用更强。最后，共纳入 162 例观察对象（A 组（n=45）、B 组（n=46）、C 组（n=39）、D 组（n=32））和 20 例正常供体作为对照。B、C 和 D 组的早期病毒学应答率分别为 58.7%、51.3%和 31.2%。24 周时，B 组（P=0.007）和 C 组（P=0.034）的 IL-1β 均高于 0 周。在 B 组中，ERG 组在 12w 和 24w 时 IL-1β 呈上升趋势。IL-1β 显著降低肝癌细胞中 HBV 的复制水平。
IL-1β 的表达增加可能增强 TDF 联合 Peg-IFN-α 治疗在 CHB 患者中实现早期应答的疗效。
